This project studies the mechanisms of lithium induced granulocytosis and assesses the clinical significance of the phenomenom by means of clinical trials in acute myelogenous leukemia (AML), severe neutropenia, and hematologic malignancies. In a randomized trial among patients receiving cytosine arabinoside - daunomycin therapy for AML the duration of neutropenia, granulocytes less than 1000/mm3 is shorter in patients receiving lithium than in controls (16.0 vs. 24.6 days, p equals .013). Therapeutic levels have been maintained without significant drug toxicity. A cooperative group trial to determine if lithium affects duration of remission or tolerance of maintenance therapy has been instituted. In patients with severe neutropenia, favorable responses to lithium (granulocyte increase greater than 300/mm3, and greater than 30% over baseline) have been seen in 11 of 23 patients with marrow failure uncomplicated by hypersplenism or acute leukemia. Our trial of lithium in patients receiving combination chemotherapy for Hodgkin's disease, lymphoma or other malignancies has been instituted but it is too early to evaluate the data. Studies of dose optimization have suggested that any lithium dose from 900 to 1500 mg/day can produce granulocytosis and that within this range, and serum levels of 0.5 to 1.5 meq/L there is no correlation of lithium level and granulocyte response.